The food industries are interested in developing functional products due to their popularity within nutritional and healthy circles. Functional fruit-based beverages represent one of the fast-growing markets due to the high concentrations of bioactive compounds (BCs), which can be health promoters. Hence, functional beverages based on citrus fruits are a potential way to take advantage of their nutritional and bioactive properties that could attract the interest of consumers. In order to ensure microbial and quality stability, the beverages are subjected to preservation treatment; however, the application of high temperatures leads to the loss of thermolabile BCs. Nowadays, innovative processing technologies (IPT) such as pulsed electric field (PEF), high-pressure processing (HPP), ultrasound processing (US), ohmic heating (OH), and microwave (MW) are a promising alternative due to their efficiency and low impact on juice BCs. The available literature concerning the effects of these technologies in functional fruit-based beverages is scarce; thus, this review gathers the most relevant information about the main positive and negative aspects of the IPT in functional properties, safety, and consumer acceptance of functional citrus-based beverages, as well as the use of citrus by-products to promote the circular economy in citrus processing.

Grapefruit (GF) processing generates significant nutrient and economic losses due to the production of 50% by-products, primarily peels. GF peels are a rich and sustainable source of bioactive compounds (BCs), such as essential oils (EOs) and phenolic compounds. Thus, finding value-added solutions based on a circular economy is paramount. This research aims to assess the antioxidant, anti-inflammatory, and antimicrobial properties of a hydroethanolic polyphenol-rich extract from crude GF peels (GF-CE), essential oil (GF-EO), and polyphenol-rich extract from GF peels after essential oil extraction (GF-PE). The GF-CE and GF-PE showed high concentrations of naringenin (7.71 and 48.60 mg/g dry extract (DE)), narirutin (15.03 and 28.73 mg/g DE), and hesperidin (0.67 and 0.29 mg/mL), respectively. Extracting firstly EOs from GF improved the release of phenolic acids (p-coumaric, ferulic, and chlorogenic acid). The GF-CE exhibited stronger free radical scavenging activity mainly in DPPH (IC50 = 75.69 ± 0.81 µg/mL) than GF-EO (1271 ± 0.85 µg/mL) and GF-PE (113.45 ± 0.85 µg/mL). The GF-EO demonstrated moderate antimicrobial activity against Gram-positive bacteria compared to the reference standard (amoxicillin) and strong activity against the yeast Candida albicans (inhibition zone of 16 mm). The major compounds in the GF-EO included D-limonene (25%), nootkatone (24%), and β-pinene (8%). Both polyphenol-rich extracts showed promising activities as COX1 and COX2 inhibitors with IC50 values of 25 ± 0.1 and 0.28 ± 0.00 µg/mL (compared to celecoxib (97.5 ± 0.1 and 0.31 ± 0.01 µg/mL) and indomethacin (6.25 ± 0.00 and 0.52 ± 0.01 µg/mL) as the standards), respectively. The study concludes that GF peels are a valuable source of BCs with significant bioactivities, offering a sustainable multi-cascade approach to recovering value-added compounds from GF peels in alignment with circular economy principles and open opportunities as functional ingredients for food applications.

Citrus peels are an important by-product of citrus processing industries, but a large part is considered waste. There has been increased attention in the last five years on these industrial by-products, especially those containing residual essential oils (EOs). Lemon, orange, and mandarin peels from Egypt were subjected to hydro-distillation to obtain EOs, which were analyzed via mass spectrometry (GC/MS) and by building Global Natural Products Social Molecular Networking (GNPS-MN) for the purpose of visually exploring the volatile components of citrus species. The constructed MN revealed that D-Limonene, α-pinene, and β-pinene are the dominant volatile constituents in the three Egyptian citrus species. The EOs from three citrus peels exhibited promising activities as antioxidants using two tested methods: 1,1-diphenyl-2-picryl-hydrazil (DPPH) and nitric oxide (NO) compared with vitamin C. Lemon EO proved excellent antimicrobial activity against Gram-positive and negative bacteria. Additionally, the three citrus EOs showed good activities against the yeast Candida albicans. Regarding the anti-inflammatory assay, the three citrus EOs showed promising activities as COX-1 and COX-2 inhibitors. This study concludes that EOs extracted from citrus peel waste can be valorized as an innovative strategy for food preservation or may be incorporated in cosmetics and pharmaceutical formulations in alignment with circular economy principles.

The rising incidence of vulvovaginal candidiasis (VVC) has been leading to the development of alternative antifungal therapies. This study aimed to develop a topical chitosan–oleic acid nanoparticle (CH-OA-NP) cream loaded with lemon peel essential oil (LPEO) for VVC treatment. The characterization of the optimal nanoparticle formulation (F4: 10 g/L CH, 2:1 OA/LPEO ratio) showed high encapsulation efficiency, stability, and controlled release. Moreover, it was characterized regarding its particle size, polydispersity index, zeta potential, and chemical/morphological profile. LPEO-related compounds (e.g., eriodictyol) were identified through LC-ESI-QqTOF-HRMS in the cream matrix, suggesting the preservation of LPEO potential bioactivities after formulation. In silico docking of 12 LPEO metabolites revealed that compounds such as citronellic acid exerted inhibitory effects against several inflammation-associated enzymes (e.g., 14-α-Demethylase). In vitro antimicrobial tests demonstrated remarkable activity against Candida albicans, Gram-negative (e.g., Escherichia coli), and Gram-positive (e.g., Staphylococcus aureus) bacteria. In vivo studies in a rat model of VVC revealed significant antifungal, anti-inflammatory, and immunomodulatory effects of the LPEO-CH-OA-NP cream (5% and 10%), leading to reduced MDA, MPO, and IL-1β levels and increased GSH activity. This novel formulation potentially offers a promising alternative therapy for VVC, addressing the current antifungal therapies’ limitations, counteracting drug resistance.

Recently, hand sanitization has gained attention for preventing disease transmission. Many on-the-market convenient dermal sanitizers contain alcohol, which can be detrimental to the skin. Therefore, three nanoemulgel formulations (LN-F1, LN-F2, LN-F3) incorporating lemon peel extract (LE), and with various increasing concentrations of xanthan gum as a gelling agent and stabilizer, were developed and characterized as a novel alternative. All formulations showed non-Newtonian shear-thinning flow behavior, particle size values below 200 nm, and increasing zeta potential with higher xanthan gum concentrations. All nanoemulgel formulations exhibited greater in vitro phenolic compound release than free LE. LN-F2 (1.0% LE, 20.0% mineral oil, 20.0% Span 80, 4.0% Cremophor RH 40, 4.0% PEG 400, 0.5% xanthan gum, 50.5% dH₂O) was selected as the optimal formulation due to improved characteristics. LE and LN-F2 potential cytotoxicity was assessed on MA-104, showing no significant cellular morphological alterations up to 10 mg/mL for both samples. LN-F2 showed in vitro antimicrobial activity against E. coli, S. Typhimurium, P. aeruginosa, S. aureus, L. monocytogenes, and C. albicans, as well as antiviral activity against phiX 174, but no effect against rotavirus (SA-11). In vivo, LN-F2 presented a removal capacity of 83% to 100% for bacteria and 89% to 100% for fungi. These findings suggest that the formulated nanoemulgel holds potential as a safe and effective antiseptic, providing a viable alternative to commercial alcohol-based formulations.